The Study Of Relationship Between Hepatic Sympathetic Regulation And Acute Liver Injury

Background:In the clinic, acute liver injury due to serious trauma, major surgery, poisoning, bacteria, virus infection may easily lead to acute liver failure. At present ,the drug treatment is hard to get an ideal effect. In this pathological process, due to trauma, bacteria, viruses, etc as a direct result of liver cell damage is limited. In fact, the body,s inappropriate inflammatory or immune response to pathogens may result in serious consequences. Excessive inflammatory response caused by a large number of inflammatory mediators in the blood circulation may end in systemic inflammatory response syndrome (SIRS) even MOSF, acute liver injury is one part of it.The occurrence and development of Inflammation is a complex process which affected by many factors regulation. Inflammatory regulation can be broadly divided into two major categories: body fluids regulation and neural regulation. At present, the research of inflammatory response and liver injury focused on fluid conditioning, the data of neural regulation show less for the lack of a good animal model. The hepatic sympathetic system was composed of three different levels: the abdominal sympathetic ganglia, thoracolumbar spinal cord, hypothalamus. Kupffer cells are the main member of mononuclear macrophage system which resident in the liver. accounting for more than 80% of the total body macrophages, 35% of liver non-parenchymal cells. The activation of Kupffer cells play an important role in acute and chronic liver inflammation.Objective :By review recent research results, our research based on the hypothesis : With the changes in sympathetic activity. sympathetic nervous system directly regulate Kupffer cell,s secretion by means of neurotransmitter release, as well as involved in start-up and trigger the excessive inflammatory response and lead to the occurrence of acute liver injury. The aims of the present study are elucidate the mechanism of inflammatory response and to propose a new perspective on the systemic inflammatory response and MOSF .methods and results:1. To observe the effects of denervation of different segment of sympathetic nerve system on liver function in the carbon tetrachloride (CCl4)induced rats and the process of synchronization associated with the inflammatory changes. From the cervical sympathetic trunk, splanchnic nerves and nerve endings in liver block the sympathetic regulation pathway, all animal model was prepared as literature reported . After 24 hours of acute liver injury model was established by using CCl4. Liver function as well as histopathological examination and other relevant indicators, serum TNF-a , neuro-electrophysiology and the norepinephrine concentrations of liver tissue were determined in each group.①Normal discharge of cervical sympathetic trunk are low amplitude, frequency uniform, voltage stabilized .After intraperitoneal injection of CCL4 ,the discharge of cervical sympathetic trunk wave V was immediate increased, pulse was enhanced and sustained record About 40 seconds later, the sympathetic nerve electrical activity back to normal .②Transection of cervical sympathetic trunk (TCST)and denervation of sympathetic nerve in liver group resulted in significant changes of parameters under acute liver injury, and has beneficial effects on protein anabolism, metabolism of bilirubin.(P < 0.05 , P < 0.01),but not transection of greater splanchnic nerve groups(P>0.05)③Compared with the shame, the liver tissue norepinephrine of TCST and sympethtic denervation in liver group were lower, the difference was significant(P<0.01)④Compared with the shame, the serum TNF-a levels of TCST and sympethtic denervation in liver group were lower, the difference was significant(P<0.01).2. To evaluate the effect of noradrenalin on the expression of TNF-αand IL-1βin rat Kupffer cells induced by lipopolysaccharide(LPS). The isolated rat kupffer cells cultured in vitro divided into three groups, Given lipopolysaccharide (10μg/ml ) with or without norepinephrine (0.1μmol / L ~ 10μmol / L) respectively for 12 hours. Using quantitative reverse transcription-polymerase chain reaction to detect TNF-a and IL-1βmRNA expression, ELISA detect TNF-a, IL-1βprotein expression of cell culture supernatant.①In the LPS and norepinephrine (1μmol / L and 10μmol / L ) group, TNF-a mRNA expression were higher than that in LPS group 50.9% (P <0 . 05) and 59.1% (P <0. 05) Respectively;IL-1βmRNA expression increased 53.7% and 57.8% than that in LPS group (P <0 . 05).②The cell culture supernatant TNF-a and IL-1βprotein were significantly higher than that in LPS group (P <0. 05) , And in low concentration (0.1μmol / L) case, the results showed no significant difference.Conclusion :1. Sympathetic system has proinflammatory effect under acute liver injury due to CCl42. The high concentration of noradrenalin could enhance the expressions of TNF-αand IL-1βof hepatic Kupffer cells induced by lipopolysaccharide and has pro-inflammatory effects. The activation of sympathetic system may direct act kupffer cells and promote the expression of inflammatory cytokines.In a certain concentration range, with the increase of norepinephrine, pro-inflammatory cytokines expression incresed as well.